Nox isoforms in vascular pathophysiology: Insights from transgenic and knockout mouse models

Elevated reactive oxygen species (ROS) formation in the vascular wall is a key feature of cardiovascular diseases and a likely contributor to oxidative stress, endothelial dysfunction and vascular inflammation. The NADPH oxidases are a family of ROS generating enzymes, of which four members (Nox1, Nox2, Nox4 and Nox5) are expressed in blood vessels. Numerous studies have demonstrated that expression and activity of at least two isoforms of NADPH oxidase - Nox1 and Nox2 - are up-regulated in animal models of hypertension, diabetes and atherosclerosis. However, these observations are merely suggestive of a role for NADPH oxidases in vessel pathology and by no means establish cause and effect. Furthermore, questions surrounding the specificity of current pharmacological inhibitors of NADPH oxidase mean that findings obtained with these compounds must be viewed with caution. Here, we review the literature on studies utilising genetically-modified mouse strains to investigate the roles of NADPH oxidases in experimental models of vascular disease.